Institute of Cellular Medicine, William Leech Building, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK;
Gut. 2011 May;60(5):680-7. doi: 10.1136/gut.2010.222133. Epub 2010 Oct 12.
The density of hepatitis C virus (HCV) in plasma is heterogeneous but the factors which influence this are poorly understood. Evidence from animal models and cell culture suggest that low-density apolipoprotein B (apoB)-associated HCV lipoviral particles (LVP) are more infectious than high-density HCV. Objective To measure LVP in patients with chronic hepatitis C genotype 1 (CHC-G1) and examine metabolic determinants of LVP load. Patients 51 patients with CHC-G1 infection.
Fasting lipid profiles and homeostasis model assessment of insulin resistance (HOMA-IR) were determined in 51 patients with CHC-G1. LVP and non-LVP viral load were measured by real-time PCR of plasma at density <1.07 g/ml and >1.07 g/ml, respectively, following iodixanol density gradient ultracentrifugation. The LVP ratio was calculated using the formula: LVP/(LVP + non-LVP).
The mean LVP ratio was 0.241 but varied 25-fold (from 0.029 to 0.74). Univariate analysis showed that the LVP ratio correlated with HOMA-IR (p=0.004) and the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio (p = 0.004), but not with apoB. In multivariate analysis, HOMA-IR was the main determinant of LVP load (log₁₀IU/ml) (R²=16.6%; p = 0.037) but the TG/HDL-C ratio was the strongest predictor of the LVP ratio (R² = 24.4%; p = 0.019). Higher LVP ratios were associated with non-response to antiviral therapy (p = 0.037) and with greater liver stiffness (p = 0.001).
IR and associated dyslipidaemia are the major determinants of low-density apoB-associated LVP in fasting plasma. This provides a possible mechanism to explain why IR is associated with more rapidly progressive liver disease and poorer treatment outcomes.
丙型肝炎病毒（HCV）在血浆中的密度是不均匀的，但影响因素知之甚少。来自动物模型和细胞培养的证据表明，低密度载脂蛋白 B（apoB）相关的 HCV 脂蛋白（LVP）比高密度 HCV 更具感染性。目的是测量慢性丙型肝炎基因型 1（CHC-G1）患者中的 LVP，并检查 LVP 负荷的代谢决定因素。患者 51 例 CHC-G1 感染患者。
测定 51 例 CHC-G1 患者的空腹血脂谱和胰岛素抵抗的稳态模型评估（HOMA-IR）。通过碘克沙醇密度梯度超速离心，分别在密度<1.07 g/ml 和>1.07 g/ml 的血浆中实时 PCR 测量 LVP 和非 LVP 病毒载量。使用公式计算 LVP 比：LVP/（LVP+非 LVP）。
平均 LVP 比为 0.241，但变化 25 倍（从 0.029 到 0.74）。单因素分析显示，LVP 比与 HOMA-IR（p=0.004）和甘油三酯/高密度脂蛋白胆固醇（TG/HDL-C）比值（p=0.004）相关，但与 apoB 无关。在多因素分析中，HOMA-IR 是 LVP 负荷（log₁₀IU/ml）的主要决定因素（R²=16.6%；p=0.037），但 TG/HDL-C 比值是 LVP 比的最强预测因子（R²=24.4%；p=0.019）。较高的 LVP 比与抗病毒治疗无反应（p=0.037）和肝硬度增加（p=0.001）相关。
IR 及其相关的血脂异常是空腹血浆中低密度 apoB 相关 LVP 的主要决定因素。这提供了一种可能的机制来解释为什么 IR 与更快进展的肝病和较差的治疗结果相关。
